Abstract
Acetyl-coenzyme A carboxylases (ACCs) play critical roles in the regulation of fatty acid metabolism and have been targeted for the development of drugs against obesity, diabetes and other metabolic diseases. Two series of compounds possessing quinoline moieties were designed, synthesized and evaluated for their potential to inhibit acetyl-CoA carboxylases. Most compounds showed moderate to good ACC inhibitory activities and compound 7a possessed the most potent biological activities against ACC1 and ACC2, with IC50 values of 189 nM and 172 nM, respectively, comparable to the positive control. Docking simulation was performed to position compound 7a into the active site of ACC to determine a probable binding model.
Highlights
Obesity is a chronic disease related to many other metabolic diseases such as type 2 diabetes mellitus (T2DM) and dyslipidemia [1,2]
Acetyl-coenzyme A carboxylases (ACCs) are key enzymes that catalyze the formation of malonyl coenzyme A (CoA), which contributes to the regulation of fatty acid biosynthesis and oxidation in humans and most other living organisms [3,4]
Inhibition of the ACCs gives the potential for managing both long chain fatty acid biosynthesis and fatty acid oxidation, which has been regarded as a novel approach to treat obesity type 2 diabetes and other diseases associated with metabolic syndrome [5]
Summary
Obesity is a chronic disease related to many other metabolic diseases such as type 2 diabetes mellitus (T2DM) and dyslipidemia [1,2]. ACC1 is a cytosolic enzyme and primarily expressed in lipogenic tissues responsible for the committed step in fatty acid biosynthesis. ACC2 is a mitochondrial enzyme that is highly expressed in oxidative tissues associated with mitochondrial fatty acid oxidation [2]. Inhibition of the ACCs gives the potential for managing both long chain fatty acid biosynthesis and fatty acid oxidation, which has been regarded as a novel approach to treat obesity type 2 diabetes and other diseases associated with metabolic syndrome [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
